This invention relates generally to devices for use in the surgical repair of heart pathologies, and, more particularly, to antimicrobial annuloplasty rings which contain relatively rigid biodegradable inserts.
Human heart valves can become deformed or otherwise damaged by any of a number of processes brought on by normal aging and/or disease pathologies. For example, degenerative diseases can cause the valve annulus to become enlarged to the point where the leaflets attached to it cannot fully close. This situation, known as valve incompetence, eventually requires surgical correction by valve repair or replacement procedures. Of the surgical options available for valve reconstruction, valvular annuloplasty represents the procedure most frequently performed, particularly for the tricuspid and mitral valves. Valvular annuloplasty is an operation whereby ring-shaped devices or bands, known as annuloplasty rings, are sewn to the distended valve annulus in order to restore it to its normal, undilated circumference.
Annuloplasty rings are most typically either highly flexible or are stiff and comparatively rigid. Rigid rings typically consists of an open wire element completely covered with cloth. The wire is somewhat stiff yet resiliently deformable and is not intended to be removable from the cloth covering. These annuloplasty rings, because of their rigidity, lie flat and maintain their somewhat oval shape during implantation. Although a rigid ring""s oval shape has been claimed to enhance the competence of the repaired valve, its rigidity can also impede the beneficial flexing movements of the native annulus during the cardiac cycle. Flexible annuloplasty rings generally consist of a soft core of elastomeric material, e.g., silicone rubber, completely enclosed by a sheath of biocompatible cloth. Because of their flexibility, these rings can be difficult to handle during surgical manipulations and generally must be supported during implantation by a holder which is subsequently removed before tying off the implanting sutures.
To overcome some of the deficiencies of flexible and rigid ring structures, an annuloplasty ring would desirably be stiff during handling and implantation, but then become flexible after implantation. As disclosed in U.S. Pat. No. 5,716,397, an annuloplasty ring may consist of a flexible ring into which a rigid structure is inserted to provide temporary rigidity during implantation. Once the ring is implanted and tested, the rigid structure may be removed. However, this approach requires undesirable additional handling after the ring is implanted. Another annuloplasty ring, as disclosed in U.S. Pat. No. 5,104,407, consists of a ring constructed partially of a flexible material and partially of a rigid material. Unfortunately, this ring will be difficult and costly to manufacture and will suffer from the drawbacks afflicting both flexible and rigid rings. In an alternative approach, Chachques et al. (Circulation 82(5), Supplement IV, 82-88, 1990) describes absorbable prosthetic rings for use in pediactric valvular annuloplasty. The rings are reported to address concerns over secondary valvular stenosis in children that can result from implantation of known annuloplasty rings. The rings described by Chachques et al. are synthesized from biodegradable polydioxanone and covered with a porous extensible sewing sheath to allow contact between the polydioxanone, the blood and the endocardium. As a result of this contact, the polydioxanone ring is reported to undergo degradation following implantation.
Colonization of microorganisms on the surfaces of annuloplasty rings and other implantable medical devices can produce serious and costly complications, including the need to remove and/or replace the implanted device and/or vigorous treatment of secondary infections. Although infection of implanted medical devices is a relatively infrequent complication associated with their clinical use, the threat to infected patients, and the cost to the medical care system, are significant.
Numerous approaches for providing antimicrobial surfaces and/or devices have been described in the art. Unfortunately, such approaches have had only limited success. For example, although coating a material with immobilized antimicrobial compounds has been reported to effectively reduce bacterial colonization of devices in a laboratory setting, similar results have been difficult to replicate in the clinical setting. To be effective in vivo, antimicrobial agents immobilized on the surface of a medical device preferably should intimately contact the colonizing bacteria that has infected the device. Unfortunately, many clinically relevant bacteria produce a slimy protective substance called biofilm within which they grow. This biofilm, among other things, prevents direct contact of the bacterial cells with a substrate surface to which they adhere, making the bacteria resistant to otherwise toxic materials that may be present on the substrate surface.
In the laboratory, the antimicrobial efficacy of medical devices that have been treated in one way or another in attempt to confer some degree of antimicrobial activity to the device, has often been evaluated by exposing the devices to bacterial cultures. The selection and source of bacteria for such testing is critical to obtaining meaningful results, since it is now known that microorganisms floating free in a cell culture (called planktonic bacteria) behave differently than those adherent to a substrate, such as a bacterial culture vessel or an implanted medical device. Planktonic bacteria are more susceptible to antimicrobial agents immobilized on a surface than are biofilm-producing bacteria. Thus, devices coated with immobilized antimicrobial agents may effectively prevent colonization of planktonic bacteria in the laboratory, but may be completely ineffective in preventing infection of devices by clinically relevant biofilm-enclosed bacteria. As a result, the experimental use of planktonic bacteria cultured in the laboratory, rather than biofilm bacteria derived from clinical infections, has led to the commercialization of numerous antimicrobial medical devices lacking clinical efficacy.
To effectively inhibit biofilm bacterial growth, an antimicrobial agent should preferably penetrate the biofilm. To achieve this, the antimicrobial agent should be able to diffuse from the surface of the medical device following implantation. Therefore, antimicrobial agents immobilized on the surface of a medical device, and therefore not subject to diffusion, have less than optimal activity against many clinically relevant microorganisms. A more effective medical device will have the ability to deliver diffusable antimicrobial agent to the local environment following implantation.
Various methods have been described for coating or otherwise incorporating antimicrobial agents into or onto medical devices in a manner which allows for their release into the local environment of an implanted medical device. For example, U.S. Pat. No. 5,624,704 reports a method for impregnating a non-metallic medical implant with an antimicrobial agent by first dissolving the antimicrobial agent in an organic solvent to form an antimicrobial composition. Thereafter, a separate penetrating agent and alkalinizing agent must be added to the antimicrobial composition. The antimicrobial composition is then applied to a medical device of interest in order to cause the incorporation of the composition into the material of the medical device. Thus, the method of U.S. Pat. No. 5,624,704 teaches the necessity of using additional components, i.e., penetrating and alkalinizing agents, in a dissolved antimicrobial composition, in order to achieve effective incorporation into the medical device. Unfortunately, the use of these additional components can substantially increase the materials and processing costs associated with such a method, and can also lead to degradation of the antimicrobial agents.
The present invention is directed to providing alternatives to the currently available annuloplasty rings which overcome, or at least reduce the effects of, one or more of the problems set forth above.
This invention provides an antimicrobial annuloplasty ring having sufficient initial rigidity, i.e., prior to implantation, to facilitate ease of handling during surgical manipulations, but which becomes flexible to a desired extent following implantation. The foregoing is accomplished by use of a relatively rigid biodegradable annuloplasty ring insert as a component of an annuloplasty ring. Upon implantation of an annuloplasty ring containing a biodegradable ring insert of this invention, the insert undergoes degradation in the patient""s body as a result of its contact with blood and/or other physiological fluids. The degradation of the biodegradable insert causes a decreasing degree of rigidity of the annuloplasty ring as the insert material is degraded and/or resorbed by the patient""s body.
Therefore, in one aspect of the present invention, there is provided an annuloplasty ring which comprises a biodegradable ring insert and a fabric sheath enclosing the ring insert, wherein the fabric sheath and/or the biodegradable insert have undergone one or more antimicrobial treatment processes. The ring insert portion of the annuloplasty ring is at least partly comprised of a biodegradable material selected from any of a variety of biodegradable polymers, including polyanhydrides, polyglycolides, polylactides, polyorthoesters, and other like materials. In one illustrative embodiment, the biodegradable insert is comprised of a highly cross-linked polyanhydride material, particularly one that is photopolymerizable, such as that produced by the photopolymerization of methacrylate anhydride monomers. The fabric sheath which encloses the biodegradable insert, or the biodegradable insert itself, is preferably treated either before, after, or simultaneous with the fabrication of the annuloplasty ring in a manner which causes the incorporation of one or more antimicrobial agents into or onto the fabric sheath.
In a further aspect of the invention, there is provided a method for making an antimicrobial annuloplasty ring by forming a biodegradable ring insert at least partly comprised of a material selected, for example, from polyanhydrides, polyglycolides, polylactides and polyorthoesters, and enclosing the ring insert within a fabric sheath. The ring insert may be formed as a solid part, may be comprised of fibrous materials, or some combination thereof, and is fabricated by any of a variety conventional techniques available for forming shaped articles from polymeric materials, including, without limitation, extrusion, molding, machining, casting, spinning, and other like processes. At some point during fabrication and/or assembly of the annuloplasty ring, or after assembly but prior to implantation, at least some portion of the ring insert and/or the fabric sheath, or some other component of the annuloplasty ring, is treated by an antimicrobial treatment process in order to cause the incorporation of at least some antimicrobial agent into or onto a desired portion or portions of the annuloplasty ring.